rs17020983

Variant names:

• chr1-207114952-C-T
• rs17020983
• NM_000715.4:c.329-464C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000715.4(C4BPA):​c.329-464C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 152,116 control chromosomes in the GnomAD database, including 5,311 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.20 (5311 hom., cov: 31)
• Consequence: C4BPA NM_000715.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.188
• Publications: 10 publications found

Genes affected

C4BPA (HGNC:1325): (complement component 4 binding protein alpha) This gene encodes a member of a superfamily of proteins composed predominantly of tandemly arrayed short consensus repeats of approximately 60 amino acids. Along with a single, unique beta-chain, seven identical alpha-chains encoded by this gene assemble into the predominant isoform of C4b-binding protein, a multimeric protein that controls activation of the complement cascade through the classical pathway. The genes encoding both alpha and beta chains are located adjacent to each other on human chromosome 1 in the regulator of complement activation gene cluster. Two pseudogenes of this gene are also found in the cluster. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C4BPA	NM_000715.4	c.329-464C>T		intron_variant	Intron 3 of 11	ENST00000367070.8	NP_000706.1
C4BPA	XM_005273251.3	c.329-464C>T		intron_variant	Intron 3 of 11		XP_005273308.1
C4BPA	XM_005273252.5	c.329-464C>T		intron_variant	Intron 3 of 11		XP_005273309.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C4BPA	ENST00000367070.8	c.329-464C>T		intron_variant	Intron 3 of 11	1	NM_000715.4	ENSP00000356037.3
C4BPA	ENST00000421786.5	c.329-464C>T		intron_variant	Intron 3 of 4	4		ENSP00000403386.1
C4BPA	ENST00000424088.1	n.*67+181C>T		intron_variant	Intron 4 of 4	4		ENSP00000395968.1

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30186 AN: 151998 Hom.: 5300 Cov.: 31

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.0604

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.0769

Gnomad OTH AF: 0.186

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.199 AC: 30224 AN: 152116 Hom.: 5311 Cov.: 31 AF XY: 0.196 AC XY: 14540 AN XY: 74360

African (AFR) AF: 0.475 AC: 19697 AN: 41454

American (AMR) AF: 0.123 AC: 1881 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 521 AN: 3470

East Asian (EAS) AF: 0.201 AC: 1042 AN: 5182

South Asian (SAS) AF: 0.131 AC: 628 AN: 4812

European-Finnish (FIN) AF: 0.0604 AC: 640 AN: 10600

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.0769 AC: 5228 AN: 68004

Other (OTH) AF: 0.184 AC: 387 AN: 2108

Alfa AF: 0.142 Hom.: 3886

Bravo AF: 0.215

Asia WGS AF: 0.195 AC: 677 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.5
DANN	Benign	0.32
PhyloP100		-0.19
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17020983; hg19: chr1-207288297;